The current tuberculosis (TB) predicament poses numerous challenges and therefore every incremental scientific work and all positive socio-political engagements, are steps taken in the right direction to eradicate TB. Progression of the late stage TB-drug pipeline into the clinics is an immediate deliverable of this global effort. At the same time, fueling basic research and pursuing early discovery work must be sustained to maintain a healthy TB-drug pipeline. This review encompasses a broad analysis of chemotherapeutic strategies that target the DNA replication, protein synthesis, cell wall biosynthesis, energy metabolism and proteolysis of Mycobacterium tuberculosis (Mtb). It includes a status check of the current TB-drug pipeline with a focus on the associated biology, emerging targets, and their promising chemical inhibitors. Potential synergies and/or gaps within or across different chemotherapeutic strategies are systematically reviewed as well.
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http://dx.doi.org/10.1016/j.trsl.2020.03.007 | DOI Listing |
Globally, drug-resistant tuberculosis (DR-TB) is responsible for 13% of mortality attributable to antimicrobial resistance. In Ethiopia, extrapulmonary tuberculosis (EPTB) is a significant public health challenge, and drug resistance (DR) in EPTB is often overlooked. In a cross-sectional study conducted between August 2022 and October 2023, we aimed to explore the magnitude of phenotypic drug resistance and identify genetic mutations linked to resistance using 189 Mycobacterium tuberculosis (MTB) isolates cultured from extrapulmonary clinical specimens.
View Article and Find Full Text PDFMicrob Pathog
January 2025
Department of Biological Sciences, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Telangana, 500037, India. Electronic address:
Tuberculosis continues to pose a health challenge causing the loss of millions of lives despite the existence of multiple drugs, for treatment. The emergence of drug-resistant strains has made the situation more complex making it increasingly difficult to fight against this disease. This review outlines the challenges associated with TB drug discovery, the nature of Mycobacterium tuberculosis shedding light on the mechanisms that lead to treatment failure and antibiotic resistance.
View Article and Find Full Text PDFTuberculosis (TB) remains among the leading infectious causes of death. Due to the limited number of antimicrobials in the TB drug discovery pipeline, interest has developed in host-directed approaches to improve TB treatment outcomes. C-C motif chemokine-like receptor 2 (CCRL2) is a unique seven-transmembrane domain receptor that is upregulated by inflammatory signals and mediates leucocyte migration.
View Article and Find Full Text PDFIndian J Microbiol
June 2024
ICMR - National Institute of Research in Tribal Health, Jabalpur, Madhya Pradesh India.
In India, drug-resistant tuberculosis (DR-TB) is a major public health issue and a significant challenge to stop TB program. An estimated 27% of new TB cases and 44% of previously treated TB cases are resistant to at least one anti-TB drug. The conventional methods for DR-TB diagnosis are time-consuming and have limitations, leading to delays in treatment initiation and the spread of the disease.
View Article and Find Full Text PDFAntimicrob Agents Chemother
August 2024
AMR Division, World Health Organization, Geneva, Switzerland.
Antimicrobial resistance (AMR) is a major global health threat estimated to have caused the deaths of 1.27 million people in 2019, which is more than HIV/AIDS and malaria deaths combined. AMR also has significant consequences on the global economy.
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